N⁶-(1-iminoethyl)-L-lysine dihydrochloride | 159190-45-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N⁶-(1-iminoethyl)-L-lysine dihydrochloride
• 英文别名: L-N⁶-(1-iminoethyl)lysine dihydrochloride；N6-(1-iminoethyl)-L-lysine, dihydrochloride；N6-(1-iminoethyl)-L-lysine dihydrochloride；L-N6-(1-iminoethyl)lysine dihydrochloride；L-N6-(1-iminoethyl)lysine hydrochloride；L-NIL；L-NIL hydrochloride；(2S)-2-amino-6-(1-aminoethylideneamino)hexanoic acid;hydrochloride
• CAS: 159190-45-1
• 化学式: C₈H₁₇N₃O₂*2ClH
• 分子量: 260.164
• InChiKey: HJYWSATZDBEAOS-FJXQXJEOSA-N

物化性质

• 溶解度：
  DMF：15mg/mL；二甲基亚砜：15mg/mL；乙醇：1mg/mL； PBS：30mg/mL；水：50mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  0.37
• 重原子数：
  14
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  102
• 氢给体数：
  4
• 氢受体数：
  4

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S37/39
• 危险类别码：
  R36/37/38
• 危险标志：
  GHS07
• 危险性描述：
  H315,H319,H335
• 危险性防范说明：
  P261,P305 + P351 + P338

制备方法与用途

生物活性

L-NIL dihydrochloride 是诱导型一氧化氮合成酶 (iNOS) 的抑制剂，其对 iNOS 的 IC50 值为 3.3 μM。

靶点

IC50:

• 3.3 μM (小鼠诱导型 NO 合成酶)
• 92 μM (大鼠脑组织稳定型 NO 合成酶)

体外研究

L-NIL 在体外对两种一氧化氮合成酶（即小鼠诱导型 NOS [miNOS] 和大鼠脑组织稳定型 NOS [rcNOS]）表现出浓度依赖性的抑制作用，且对 miNOS 的选择性更强。其 IC50 值分别为 3.3 μM 和 92 μM，说明 L-NIL 对 miNOS 的选择性为 28 倍。此外，L-NIL 在体外的效力比 L-NMA 或 L-NNA 高约 6 倍。

体内研究

在小鼠肾脏缺血再灌注 (IR) 引起的炎症、氧化应激和自噬模型中，使用 L-NIL（10 和 30 mg/kg 腹腔注射）能够有效预防上述现象。具体表现为：

• 小鼠血浆 NGAL 水平显著增加；
• TLR4 和 IL1β 等蛋白含量显著减少，clustin 转录本水平下降；
• NFAT5 mRNA 表达量显著升高；
• AR 蛋白表达量显著降低。

实验数据表明 L-NIL 在体内具有良好的治疗效果。

反应信息

• 作为产物：
  描述：

  N-alpha-叔丁氧羰基-L-赖氨酸 在 盐酸 、 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 19.0h， 生成 N⁶-(1-iminoethyl)-L-lysine dihydrochloride
  参考文献：
  名称：

  L-N6-(1-Iminoethyl)lysine: A Selective Inhibitor of Inducible Nitric Oxide Synthase

  摘要：

  L-N-6-(1-Iminoethyl)lysine (L-NIL) has been synthesized and is shown to be both a potent and selective inhibitor of mouse inducible nitric oxide synthase (miNOS). L-NIL has an IC50 of 3.3 mu M for miNOS compared to an IC50 of 92 mu M for rat brain constitutive NO indicating that L-NIL is 28-fold more selective for inducible NOS. L-N-5-(1-Iminoethyl)ornithine (L-NIO), which differs from L-NIL by having one less methylene group, has very similar potency for inducible NOS, but lacks selectivity. DL-N-7-(1-Iminoethyl)homolysine was also synthesized and found to be substantially less potent than L-NIL or L-NIO, with intermediate selectivity for inducible NOS, These data suggest that L-NIL may be useful as a selective inhibitor of inducible NOS for determining the role of this enzyme in disease models.

  DOI：

  10.1021/jm00049a007

文献信息

• Amidino derivatives and their use as nitric oxide synthase inhibitors
  申请人：Glaxo Wellcome Inc.

  公开号：US05863931A1

  公开（公告）日：1999-01-26

  Amidino derivatives of formula (I) and salts, and pharmaceutically acceptable esters and amides thereof, in which: R.sup.1 is a C.sub.1-6 straight or branched chain alkyl group, a C.sub.2-6 alkenyl group, a C.sub.2-6 alkynyl group, a C.sub.3-6 cycloalkyl group or a C.sub.3-6 cycloalkylC.sub.1-6 alkyl group; Q is an alkylene, alkenylene or alkynylene group having 3 to 6 carbon atoms and which may optionally be substituted by one or more C.sub.1-3 alkyl groups; a group of formula --(CH.sub.2).sub.p X(CH.sub.2).sub.q -- where p is 2 or 3, q is 1 or 2 and X is S(O).sub.x where x is 0, 1 or 2, O or NR.sup.2 where R.sup.2 is H or C.sub.1-6 alkyl; or a group of formula --(CH.sub.2).sub.r A(CH.sub.2).sub.s -- where r is 0, 1 or 2, s is 0, 1 or 2 and A is a 3 to 6 membered carbocyclic or heterocyclic ring which may optionally be substituted by one or more suitable substituents such as C.sub.1-6 alkyl, C.sub.1-6 alkoxy, hydroxy, halo, nitro, cyano, trifluoro C.sub.1-6 alkyl, amino, C.sub.1-6 alkylamino or diC.sub.1-6 alkylamino; and pharmaceutical formulations containing them are described for use in medicine novel compounds of formula (I) and the preparation of such novel compounds are also disclosed.

  公式（I）中的Amidino衍生物及其盐，药学上可接受的酯和酰胺，其中：R.sup.1是C.sub.1-6直链或支链烷基，C.sub.2-6烯基，C.sub.2-6炔基，C.sub.3-6环烷基或C.sub.3-6环烷基C.sub.1-6烷基；Q是具有3至6个碳原子的烷基，烯基或炔基，可选择地被一个或多个C.sub.1-3烷基取代；公式--（CH.sub.2）.sub.pX（CH.sub.2）.sub.q--的基团，其中p为2或3，q为1或2，X为S（O）.sub.x，其中x为0，1或2，O或NR.sup.2，其中R.sup.2为H或C.sub.1-6烷基；或公式--（CH.sub.2）.sub.rA（CH.sub.2）.sub.s--的基团，其中r为0，1或2，s为0，1或2，A为3至6个成员的碳环或杂环，可选择地被一个或多个适当的取代基如C.sub.1-6烷基，C.sub.1-6烷氧基，羟基，卤素，硝基，氰基，三氟甲基C.sub.1-6烷基，氨基，C.sub.1-6烷基氨基或二C.sub.1-6烷基氨基取代；并描述了包含它们的制药配方用于医学中的新型化合物的制备。
• Amniotic membrane preparations and purified compositions and methods of use
  申请人：TissueTech, Inc.

  公开号：EP2664337A1

  公开（公告）日：2013-11-20

  Compositions having a combination of specific biological components have been found to exert a number of useful effects in mammalian cells, including modulating TGF-ß signalling, apoptosis, and proliferation of mammalian cells, as well as decreasing inflammation in mice. These components can be obtained commercially, or can be prepared from biological tissues such as placental tissues. Placental amniotic membrane (AM) preparations described herein include AM pieces, AM extracts, AM jelly, AM stroma, and mixtures of these compositions with additional components. The compositions can be used to treat various diseases, such as wound healing, inflammation and angiogenesis-related diseases.

  研究发现，具有特定生物成分组合的复合物可在哺乳动物细胞中发挥多种有益作用，包括调节哺乳动物细胞的 TGF-ß 信号、凋亡和增殖，以及减轻小鼠的炎症反应。这些成分可以通过商业途径获得，也可以从胎盘组织等生物组织中制备。本文所述的胎盘羊膜（AM）制剂包括AM片、AM提取物、AM胶冻、AM基质以及这些成分与其他成分的混合物。这些组合物可用于治疗各种疾病，如伤口愈合、炎症和血管生成相关疾病。
• L-N6-(1-Iminoethyl)lysine: A Selective Inhibitor of Inducible Nitric Oxide Synthase
  作者：William M. Moore、R. Keith Webber、Gina M. Jerome、Foe S. Tjoeng、Thomas P. Misko、Mark G. Currie

  DOI：10.1021/jm00049a007

  日期：1994.11

  L-N-6-(1-Iminoethyl)lysine (L-NIL) has been synthesized and is shown to be both a potent and selective inhibitor of mouse inducible nitric oxide synthase (miNOS). L-NIL has an IC50 of 3.3 mu M for miNOS compared to an IC50 of 92 mu M for rat brain constitutive NO indicating that L-NIL is 28-fold more selective for inducible NOS. L-N-5-(1-Iminoethyl)ornithine (L-NIO), which differs from L-NIL by having one less methylene group, has very similar potency for inducible NOS, but lacks selectivity. DL-N-7-(1-Iminoethyl)homolysine was also synthesized and found to be substantially less potent than L-NIL or L-NIO, with intermediate selectivity for inducible NOS, These data suggest that L-NIL may be useful as a selective inhibitor of inducible NOS for determining the role of this enzyme in disease models.
• AMNIOTIC MEMBRANE PREPARATIONS AND PURIFIED COMPOSITIONS AND METHODS OF USE
  申请人：TissueTech, Inc.

  公开号：EP1933852B1

  公开（公告）日：2018-12-19
• Amniotic membrane preparations and purified compositions and anti-inflammation methods
  申请人：Tseng Scheffer

  公开号：US20070231401A1

  公开（公告）日：2007-10-04

  Compositions having a combination of specific biological components have been found to exert a number of useful effects in mammalian cells, including modulating TGF β signaling, apoptosis, and proliferation of mammalian cells, as well as decreasing inflammation in mice. These components can be obtained commercially, or can be prepared from biological tissues such as placental tissues. Placental amniotic membrane (AM) preparations described herein include AM pieces, AM extracts, AM jelly, AM stroma, and mixtures of these compositions with additional components. The compositions can be used to treat various diseases, such as wound healing, inflammation and angiogenesis-related diseases.